Idiopathic Pulmonary Fibrosis (IPF) is a chronic and progressive fibrosing interstitial lung disease with an unknown etiology. Diagnosis of IPF is based on clinical and radiological features and, when available, findings of usual interstitial pneumonia on lung biopsy. IPF patients have an overall median survival of 3-3.5 years. The disease is more prevalent and probably more lethal among males.3, 4 With the exception of lung transplantation, no therapy has been proven beneficial for IPF.
The course of IPF is highly variable and largely unpredictable among individual patients. Disease progression in current clinical practice is monitored by pulmonary function tests [e.g., forced vital capacity (FVC), diffusion capacity for carbon monoxide (DLCO)]; high resolution CT scans (HRCT) and, measures of oxygenation. Previous studies have shown associations of serial measures of these clinical variables with disease extent and poor outcomes. The available evidence suggests that plasma protein concentrations and other blood cells may be of diagnostic use and to be indicative of disease severity and outcome prediction in IPF patients.
Identification of biomarkers may facilitate the diagnosis and follow-up of patients with IPF as well as the implementation of new therapeutic interventions. Currently, establishing a diagnosis of IPF may require surgical lung biopsy in patients with atypical clinical presentations or high-resolution computed tomography (HRCT) scans. Patients with IPF are often evaluated by serial pulmonary physiology measurements and repeated radiographic examinations. These studies provide a general assessment of the extent of disease, but do not provide information about disease activity on a molecular level. Higher plasma concentrations of surfactant proteins KL-6, FASL, CCL-2, α-defensins, and most recently SPP1 have been reported in patients with IPF and other ILDs but most of these studies were modest in size and assayed only a single or a few protein markers simultaneously. Matrix metalloproteinase-8 (“MMP8”) has been implicated as playing a role in tissue remodeling in IPF, but also in sarcoidosis, making it a nonspecific marker of IPF. Similarly, matrix metalloproteinase-7 (“MMP7”) was reported to be elevated in bronchoalveolar fluid from both IPF patients as well as patients suffering from cryptogenic organizing pneumonia (“COP”).
More recently, certain panels of markers for diagnosing and evaluating the severity and/or progression of IPF have been proposed. Those panels are based, at least in part, on the discovery that identifying increases in the plasma levels of MMP7, MMP1 and MMP8, as well as IGFBP1 and/or TNFRSF1A, indicates a diagnosis of IPF with a high degree of sensitivity and specificity.